Construction of ROS-responsive hydrogen sulfide donor-antioxidant enzyme composite nanosystem and its application in the treatment of ischemia-reperfusion liver injury

• 1、College of Pharmacy, Chongqing University, Chongqing 401331

Abstract：This study aimed to address the ROS burst, amplified inflammation, and cellular damage involved in hepatic ischemia-reperfusion injury (HIRI). A ROS-responsive hydrogen sulfide donor, NHB, was designed and synthesized, and a composite nanosystem, NHB@SOD/CAT, loaded with superoxide dismutase and catalase, was successfully constructed. The results showed that this nanosystem possessed favorable particle characteristics, stability, and protein-loading capacity, and could undergo ROS-responsive degradation with sustained H2S release under oxidative conditions. In vitro experiments demonstrated that NHB@SOD/CAT had good biocompatibility, significantly improved the viability of hepatocytes after hypoxia/reoxygenation injury, and effectively reduced intracellular ROS levels. In vivo studies further confirmed that the nanosystem markedly alleviated hepatic necrosis and histopathological damage, improved oxidative stress and inflammatory responses, and promoted macrophage polarization toward an anti-inflammatory phenotype. Overall, NHB@SOD/CAT effectively attenuated HIRI through the synergistic effects of controlled H2S release and antioxidant enzyme delivery, providing a promising strategy for HIRI treatment.

Keywords： hepatic ischemia-reperfusion injury hydrogen sulfide donor antioxidant enzymes ROS responsiveness synergistic therapy